JP2000185094A - Leukocyte selective removal filter device - Google Patents
Leukocyte selective removal filter deviceInfo
- Publication number
- JP2000185094A JP2000185094A JP10375883A JP37588398A JP2000185094A JP 2000185094 A JP2000185094 A JP 2000185094A JP 10375883 A JP10375883 A JP 10375883A JP 37588398 A JP37588398 A JP 37588398A JP 2000185094 A JP2000185094 A JP 2000185094A
- Authority
- JP
- Japan
- Prior art keywords
- blood
- selective removal
- less
- hollow cylindrical
- leukocyte
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、多量の血液中より
白血球を選択的に除去するための白血球選択除去フィル
ター装置に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a leukocyte selective removal filter device for selectively removing leukocytes from a large amount of blood.
【０００２】[0002]
【従来の技術】近年、全身性エリテマトーデス、慢性又
は悪性関節リウマチ、多発性硬化症、潰瘍性大腸炎、ク
ローン病等の自己免疫疾患、炎症性腸疾患、白血病、癌
などの治療、或いは臓器移植手術前の免疫抑制の目的で
血液中の白血球を選択的に除去する技術の要求が高まっ
ている。これらの用途に用いられる白血球選択除去フィ
ルター装置においては、高い白血球除去能力はもちろん
のこと、１Ｌ以上７Ｌ未満の血液処理能力を合わせ持つ
ことが要求されている。更にこれに加えて、赤血球、血
小板等の他の細胞の高い回収が同時に要求されている。
現在、白血球除去を目的とした白血球選択除去フィルタ
ー装置としては、極細繊維からなる平板型の不織布フィ
ルターがよく知られている。しかしながら、上記のよう
な多量の血液をこれらの平板型フィルターにより処理し
ようとすると、圧力損失を低く抑えるためにかなり大き
な濾過断面積が必要であり操作性という使用面からも容
器の成型・組立てという製造面からもあまり実用的でな
い。そこで、上記目的のために、フィルターを円筒形状
に巻いたものが知られいる（特開昭６２−２４３５６１
号公報）。しかしながら、ここに開示されたフィルター
装置では、除去効率を高めるために血液との接触面積が
非常に大きい捕捉材をフィルターとして用いているため
に、血液とフィルター表面との急激な接触により、血液
凝固成分が活性化し以下のような問題を生じる可能性が
あり得ると考えられる。即ち、血栓がフィルター表面を
閉塞してしまうためフィルター装置内で血液の流れが悪
くなってしまい、同時に血小板の活性化も併発してしま
い、結果として血小板回収率が低下してしまうという問
題点がある。一方、血小板の高回収を目的に、表面にポ
リエチレングリコールを固定したフィルターが、特開平
１０ー３３６６８号公報で提案されているが、そのまま
大量処理に用いることは困難を伴うと考えられる。以上
のような理由から、多量の血液を効率的に処理するため
のコンパクトで、操作性が良く、かつ高い血小板回収性
を有する白血球選択除去フィルター装置の開発が望まれ
ていた。In recent years, treatment of autoimmune diseases such as systemic lupus erythematosus, chronic or malignant rheumatoid arthritis, multiple sclerosis, ulcerative colitis, Crohn's disease, inflammatory bowel disease, leukemia, cancer, or organ transplantation There is an increasing demand for a technique for selectively removing leukocytes in blood for the purpose of immunosuppression before surgery. The filter device for selectively removing leukocytes used in these applications is required to have not only a high leukocyte removal capability but also a blood processing capability of 1 L or more and less than 7 L. In addition to this, a high recovery of other cells such as red blood cells, platelets and the like is also required at the same time.
At present, a plate-type nonwoven fabric filter made of ultrafine fibers is well known as a leukocyte selective removal filter device for the purpose of leukocyte removal. However, if a large amount of blood as described above is to be processed by these flat filters, a considerably large filtration cross-sectional area is required in order to suppress pressure loss, and from the viewpoint of operability, it is necessary to mold and assemble a container. Not very practical from a manufacturing perspective. Therefore, a filter in which a filter is wound into a cylindrical shape for the above purpose is known (JP-A-62-243561).
No.). However, in the filter device disclosed herein, since a capturing material having a very large contact area with blood is used as a filter in order to increase the removal efficiency, a rapid contact between blood and the filter surface causes blood coagulation. It is believed that the components may be activated and cause the following problems. That is, the thrombus blocks the filter surface, so that the blood flow in the filter device is deteriorated, and at the same time, platelet activation is concurrently caused, resulting in a decrease in the platelet recovery rate. is there. On the other hand, a filter having polyethylene glycol immobilized on its surface for the purpose of high platelet recovery has been proposed in Japanese Patent Application Laid-Open No. Hei 10-33668, but it is considered that it is difficult to directly use it for mass processing. For the reasons described above, there has been a demand for the development of a compact and easy-to-operate leukocyte removal filter device for efficiently processing a large amount of blood and having high platelet recovery.
【０００３】[0003]
【発明が解決しようとする課題】本発明は、上記の問題
点に鑑み、血液中の凝固成分の活性化に伴うフィルター
部分の閉塞を抑制し、血小板の回収性を下げることなく
多量の血液から白血球を選択的に除去できる白血球選択
除去フィルター装置を提供することを課題とする。SUMMARY OF THE INVENTION In view of the above problems, the present invention suppresses blockage of a filter portion due to activation of a coagulation component in blood, and enables a large amount of blood to be collected without lowering platelet recovery. An object of the present invention is to provide a leukocyte selective removal filter device capable of selectively removing leukocytes.
【０００４】[0004]
【課題を解決するための手段】本発明は、上記課題を達
成するために、下記の構成を有する。即ち、平均繊維直
径が０．３μｍ以上１０．０μｍ未満であり、かつ繊維
の表面にポリエチレングリコール鎖を有するモノマー単
位が共有結合により固定されている不織布からなる白血
球選択除去フィルター層に血液の流通が可能なシート状
のスペーサー材が積層されて反物状に円筒形状に巻かれ
てなる中空円筒状フィルター材が、その両端面を封止さ
れた状態で血液入口と血液出口とを有する円筒状容器に
納められてなる白血球選択除去フィルター装置であっ
て、容器の血液入口は前記中空円筒状フィルター材の外
周面に通じる部位に、また容器の血液出口は前記中空円
筒状フィルター材の内周面に通じる部位にそれぞれ設け
られており、且つ前記スペーサー材は前記中空円筒状フ
ィルター材外周面に少なくともその外周端部を露出させ
ていることを特徴とする白血球選択除去フィルター装置
である。本発明でいう白血球選択除去フィルター層と
は、血液中の白血球を選択的に捕捉するが、他の血液成
分は捕捉し難いフィルター単層、或いは複数のフィルタ
ーを積層した層である。白血球選択除去フィルター層の
形態としては、除去効率という観点から不織布が好まし
い結果を与える。不織布とは、一層以上の繊維の塊を製
編織しないで布状構造としたものをいう。繊維の素材と
しては、ポリプロピレン、ポリエチレン、ポリエチレン
テレフタレート、ポリブチレンテレフタレート、ポリア
クリルアミド、ポリアクリロニトリル等の合成繊維、無
機繊維等が用いられる。中でもポリエチレン、ポリプロ
ピレン等のポリオレフィン、ポリオレフィンのブレンド
及び／又は重合体等の繊維が好ましく用いられる。更に
血小板の回収性を高めるため、本発明では、これら不織
布を構成する繊維の表面にポリエチレングリコール鎖を
有するモノマー単位が共有結合により固定されている必
要がある。ポリエチレングリコール鎖を有するモノマー
を共有結合で固定する方法としては、放射線によるグラ
フト重合が好ましく用いられる。放射線によるグラフト
重合は、不織布とモノマーに同時に放射線を照射する同
時重合法、予め不織布に放射線を照射し、表面にラジカ
ルを発生させた後にモノマーを添加することでグラフト
する後重合、放射線を照射して表面に活性種を生成さ
せ、活性種よりグラフトを開始するポスト開始重合等の
方法が良好に用いられる。用いる放射線の種類はアルフ
ァ線、ベータ線、ガンマ線、電子線、紫外線等のいずれ
も用いることができるが、中でもグラフト効率の点でガ
ンマ線、電子線が好ましく用いられる。更には、表面の
みの照射を可能とする電子線が最も好ましく用いられ
る。The present invention has the following configuration to achieve the above object. That is, blood flows through a leukocyte selective removal filter layer made of a nonwoven fabric having an average fiber diameter of 0.3 μm or more and less than 10.0 μm, and a monomer unit having a polyethylene glycol chain on the surface of the fiber fixed by covalent bonds. A hollow cylindrical filter material in which a possible sheet-like spacer material is laminated and wound into a cylindrical shape in the shape of a piece, in a cylindrical container having a blood inlet and a blood outlet with both end surfaces sealed. A leukocyte selective removal filter device contained therein, wherein a blood inlet of the container communicates with a portion communicating with an outer peripheral surface of the hollow cylindrical filter material, and a blood outlet of the container communicates with an inner peripheral surface of the hollow cylindrical filter material. And the spacer material has at least an outer peripheral end thereof exposed on the outer peripheral surface of the hollow cylindrical filter material. A filter for selectively removing leukocytes. The leukocyte selective removal filter layer as referred to in the present invention is a filter single layer which selectively captures leukocytes in blood but hardly captures other blood components, or a layer in which a plurality of filters are laminated. As the form of the leukocyte selective removal filter layer, a nonwoven fabric gives a preferable result from the viewpoint of removal efficiency. Nonwoven fabric refers to a nonwoven fabric having a cloth-like structure without knitting or weaving one or more lump of fibers. As a fiber material, synthetic fibers such as polypropylene, polyethylene, polyethylene terephthalate, polybutylene terephthalate, polyacrylamide, and polyacrylonitrile, and inorganic fibers are used. Above all, fibers such as polyolefins such as polyethylene and polypropylene, and blends and / or polymers of polyolefins are preferably used. In order to further enhance the recoverability of platelets, in the present invention, it is necessary that a monomer unit having a polyethylene glycol chain be immobilized on the surface of the fibers constituting the nonwoven fabric by a covalent bond. As a method of fixing a monomer having a polyethylene glycol chain by a covalent bond, graft polymerization by radiation is preferably used. Graft polymerization by radiation is a simultaneous polymerization method of irradiating radiation to the nonwoven fabric and the monomer at the same time, irradiating radiation to the nonwoven fabric in advance, generating radicals on the surface, then grafting by adding the monomer, and then polymerizing and irradiating radiation. For example, a method such as post-initiated polymerization in which active species are generated on the surface to initiate grafting from the active species is preferably used. As the type of radiation to be used, any of alpha rays, beta rays, gamma rays, electron beams, and ultraviolet rays can be used. Among them, gamma rays and electron beams are preferably used in terms of graft efficiency. Further, an electron beam capable of irradiating only the surface is most preferably used.
【０００５】ポリエチレングリコール鎖を有するモノマ
ーは、ポリエチレングリコール鎖及び、重合可能な官能
基を有するモノマーであれば、いずれも用いることがで
きる。好ましいモノマーを例示すると、メトキシジエチ
レングリコールメタクリレート、メトキシトリエチレン
グリコールメタクリレート、メトキシテトラエチレング
リコールメタクリレート等のエチレングリコール単位の
繰り返しが２以上のメトキシポリエチレングリコールメ
タクリレート類、或いは重合可能な官能基がアクリレー
ト化したアクリレート類、更にポリエチレングリコール
の末端が水酸基であるメタクリレート或いはアクリレー
ト類等が好ましく用いられる。重合性の点より、これら
ポリエチレングリコール鎖のグリコール繰り返し単位は
２以上１０未満が最も好ましく用いられる。重合性の点
から、更に好ましくは、２以上８未満、最も好ましくは
２以上６未満の時良好に用いられる。As the monomer having a polyethylene glycol chain, any monomer having a polyethylene glycol chain and a polymerizable functional group can be used. Preferred examples of the monomer include methoxydiethylene glycol methacrylate, methoxytriethylene glycol methacrylate, methoxytetraethylene glycol methacrylate, and other methoxypolyethylene glycol methacrylates having two or more repeating ethylene glycol units, or acrylates having a polymerizable functional group acrylated. Further, methacrylates or acrylates in which the terminal of polyethylene glycol is a hydroxyl group are preferably used. From the viewpoint of polymerizability, the number of glycol repeating units of these polyethylene glycol chains is preferably 2 or more and less than 10. From the viewpoint of polymerizability, more preferably, it is 2 or more and less than 8, most preferably 2 or more and less than 6.
【０００６】不織布を構成する繊維の平均直径は、０．
３μｍ以上１０．０μｍ未満、好ましくは、０．３μｍ
以上５μｍ未満、より好ましくは０．５μｍ以上５．０
μｍ未満が良い。平均直径が０．３μｍより小さくなる
と血液の流動性が悪くなって装置内で滞留等が発生し血
小板活性化を起こしやすくなり、１０．０μｍより大き
いと白血球除去率が悪くなってしまうため好ましくな
い。本発明にいう不織布を構成する繊維の平均直径は、
例えば不織布を構成している繊維の走査型電子顕微鏡写
真を撮り、無作為に選択した１００本以上の繊維の直径
を測定し、それらを数平均する方法で求められる。本発
明に用いられる白血球選択除去フィルター層の厚みは、
０．１ｍｍ以上５．０ｍｍ未満が望ましい。０．５ｍｍ
よりも厚みが大きい白血球選択除去フィルター層を反物
状に巻く場合、必然的に実効濾過面積が小さくなるため
好ましくない。一方、厚みが０．１ｍｍより小さい場
合、実効濾過面積は大きくなるが、血液の濾過長が不足
し、白血球除去能が悪くなってしまうため好ましくな
い。また、白血球の総除去量は白血球選択除去フィルタ
ー層の重量に依存して大きくなる。従って１Ｌ以上７Ｌ
未満の血液を処理する場合、好ましい白血球選択除去フ
ィルター層の重量は１０ｇ以上１５０ｇ未満である。よ
り好ましくは、１０ｇ以上１００ｇ未満、最も好ましく
は１５ｇ以上５０ｇ未満である。白血球選択除去フィル
ター層の重量が１０ｇ未満では、白血球の除去量が少な
いため好ましくない。白血球選択除去フィルター層の重
量が１５０ｇ以上では、過剰なため、血小板の吸着を起
こし、更に過大な大きさの容器を必要とするため実用的
でない。本発明に言う選択性は、血液を１Ｌ以上７Ｌ未
満処理する場合、白血球除去率は８０％以上１００％以
下、このときの血小板回収率は６０％以上１００％以下
であることが好ましい。本発明の白血球選択除去フィル
ター装置においては、主機能である白血球除去率は、出
来るだけ高いことが好ましい。一方血小板回収率も出来
るだけ高い方が好ましい。従って、更に好ましい白血球
除去率は８５％以上１００％以下、このときの血小板回
収率は７０％以上１００％以下、最も好ましくは、白血
球除去率９０％以上１００％以下、血小板回収率８０％
以上１００％以下である。[0006] The average diameter of the fibers constituting the nonwoven fabric is 0.
3 μm or more and less than 10.0 μm, preferably 0.3 μm
Not less than 5 μm, more preferably not less than 0.5 μm and 5.0.
Less than μm is good. When the average diameter is smaller than 0.3 μm, the blood fluidity deteriorates and stagnation or the like occurs in the apparatus and platelet activation is easily caused. When the average diameter is larger than 10.0 μm, the leukocyte removal rate deteriorates, which is not preferable. . The average diameter of the fibers constituting the nonwoven fabric according to the present invention,
For example, a scanning electron microscope photograph of the fibers constituting the nonwoven fabric is taken, the diameter of 100 or more randomly selected fibers is measured, and the number is averaged. The thickness of the leukocyte selective removal filter layer used in the present invention,
Desirably, it is 0.1 mm or more and less than 5.0 mm. 0.5mm
It is not preferable to wind the leukocyte selective removal filter layer having a thickness larger than that of the filter layer, since the effective filtration area necessarily becomes small. On the other hand, when the thickness is less than 0.1 mm, the effective filtration area becomes large, but the filtration length of blood is insufficient, and the leukocyte removal ability is deteriorated, which is not preferable. In addition, the total amount of leukocytes removed increases depending on the weight of the leukocyte selective removal filter layer. Therefore, 1L or more and 7L
When processing less than less blood, the preferred weight of the leukocyte selective removal filter layer is 10 g or more and less than 150 g. More preferably, it is 10 g or more and less than 100 g, and most preferably 15 g or more and less than 50 g. If the weight of the filter layer for selectively removing leukocytes is less than 10 g, the amount of leukocytes removed is undesirably small. If the weight of the leukocyte selective removal filter layer is 150 g or more, it is not practical because it is excessive and causes adsorption of platelets and further requires an excessively large container. The selectivity referred to in the present invention is that when blood is treated with 1 L or more and less than 7 L, the leukocyte removal rate is preferably 80% or more and 100% or less, and the platelet collection rate at this time is preferably 60% or more and 100% or less. In the leukocyte selective removal filter device of the present invention, the leukocyte removal rate, which is the main function, is preferably as high as possible. On the other hand, it is preferable that the platelet collection rate is as high as possible. Accordingly, the leukocyte removal rate is more preferably 85% or more and 100% or less, and the platelet collection rate at this time is 70% or more and 100% or less, most preferably, the leukocyte removal rate is 90% or more and 100% or less, and the platelet collection rate is 80%.
Not less than 100%.
【０００７】本発明にいうスペーサー層とは、白血球選
択除去フィルター層よりも血液がより流れやすい層であ
り、目の粗い網状の金属や合成樹脂、無機繊維、合成繊
維、或いは白血球選択除去フィルター層に使用される不
織布よりも平均繊維径の大きな不織布なども用いられ
る。スペーサー層は白血球選択除去フィルター層間に血
液の流れやすい部分を確保するために白血球選択除去フ
ィルター層に積層されて反物状に一緒に巻かれるもので
ある。なお、本発明において、スペーサー層とは白血球
選択除去フィルター層間に挟まれた部分のみを言い、白
血球選択除去フィルター層間に挟まれずに露出した部分
は含まない。また、スペーサー層は少なくともその外周
端部を白血球選択除去フィルター材の外周面に露出させ
ていることが必要である。白血球選択除去フィルター層
の外周面が全面に渡って前述の不織布からなる白血球選
択除去フィルター層で構成されていると、スペーサー層
への流路確保が不十分となる。スペーサー層の厚みは白
血球選択除去フィルター層の厚みや積層数にも左右され
るが、０．５ｍｍ以上３．０ｍｍ未満、好ましくは、
０．６ｍｍ以上３．０ｍｍ未満、より好ましくは、０．
７ｍｍ以上２．０ｍｍ未満が良い。スペーサー層の厚み
が０．５ｍｍ未満になると、血液のスペーサー方向への
流路が十分確保出来ないため好ましくない。また厚みが
３．０ｍｍより大きくなると白血球選択除去フィルター
層の量が相対的に少なくなってしまうため、大量の血液
を処理する場合、大きなプライミングボリュームを必要
とし、好ましくない。本発明の白血球選択除去フィルタ
ー層がスペーサー材と接触することによって生じる面積
は、血液の濾過長と処理効率を規定する上で重要であ
る。白血球除去フィルター層がスペーサー材と接触する
面積は片側の面積として５００ｃｍ2以上５０００ｃｍ2
未満であれば実用上良好に用いられる。５００ｃｍ2未
満であると１Ｌ以上７Ｌ未満の血液を処理する場合、白
血球の除去率が減少するため好ましくない。断面積が５
０００ｃｍ2以上では、容器容量が大きくなるため実用
的ではない。好ましくは１０００ｃｍ2 以上４０００ｃ
ｍ2 未満、最も好ましくは、１０００ｃｍ2 以上３００
０ｃｍ2未満である。[0007] The spacer layer referred to in the present invention is a layer through which blood flows more easily than a leukocyte selective removal filter layer. The spacer layer is a coarse mesh-like metal or synthetic resin, inorganic fiber, synthetic fiber, or leukocyte selective filter layer. Nonwoven fabrics having an average fiber diameter larger than the nonwoven fabric used in the above method are also used. The spacer layer is laminated on the leukocyte selective removal filter layer and wrapped together in a reverse shape in order to secure a portion where blood easily flows between the leukocyte selective removal filter layers. In the present invention, the spacer layer means only a portion sandwiched between the leukocyte selective removal filter layers, and does not include a portion exposed without being sandwiched between the leukocyte selective removal filter layers. It is necessary that at least the outer peripheral end of the spacer layer is exposed on the outer peripheral surface of the filter material for selectively removing leukocytes. If the outer peripheral surface of the leukocyte selective removal filter layer is entirely composed of the leukocyte selective filter layer made of the above-mentioned nonwoven fabric, it is insufficient to secure a flow path to the spacer layer. Although the thickness of the spacer layer depends on the thickness and the number of layers of the leukocyte selective removal filter layer, it is 0.5 mm or more and less than 3.0 mm, preferably,
0.6 mm or more and less than 3.0 mm, more preferably 0.
It is preferably 7 mm or more and less than 2.0 mm. If the thickness of the spacer layer is less than 0.5 mm, it is not preferable because a sufficient flow path for the blood in the spacer direction cannot be secured. On the other hand, if the thickness is larger than 3.0 mm, the amount of the leukocyte selective removal filter layer becomes relatively small, so that when processing a large amount of blood, a large priming volume is required, which is not preferable. The area generated by the contact of the leukocyte selective removal filter layer of the present invention with the spacer material is important in defining the blood filtration length and the processing efficiency. Area leukocyte removal filter layer is in contact with the spacer member is 500 cm 2 or more as one side of the area 5000 cm 2
If it is less than this, it can be used practically well. When the blood volume is less than 500 cm 2 , the rate of leukocyte removal decreases when processing 1 L or more and less than 7 L of blood. Cross section is 5
If it is 000 cm 2 or more, it is not practical because the container capacity increases. Preferably 1000cm 2 or more and 4000c
m 2 , most preferably 1000 cm 2 or more and 300
It is less than 0 cm 2 .
【０００８】また、白血球選択除去フィルター層の中央
の中空部位には、白血球選択除去フィルター層の内周面
を押さえ、中空空間を確保させるために、メッシュや多
孔部分を有するパイプなどからなる、白血球選択除去フ
ィルター層内周面に接する支持体を設けることが好まし
い。また、白血球選択除去フィルター層の中空部の大き
さは、白血球選択除去フィルター層の大きさ、即ち白血
球選択除去フィルター層の外径や厚み等に応じて適宜決
定される。本発明において、白血球選択除去フィルター
層はほぼ同様な円筒状の容器に納められ、両端部は血液
が通れないように液密に封止される。封止には血液に接
触した際の適合性に優れ、且つ封止に適した液漏れしな
い材質のものを用いる。具体的にはウレタンなどの公知
の合成樹脂が使用できる。血液入口は、両端が封止され
た白血球選択除去フィルター層の外周面側に被処理血液
を供給し得る位置であれば、容器の任意の位置に設けて
よいが、被処理血液が白血球選択除去フィルター層の外
周面へ均等に流れ込み、白血球選択除去フィルター層が
効率的に利用されるために被処理血液が放射状に分散さ
れるように円筒状容器の天井部に設けるのが好ましい。
血液出口は中空円筒状白血球選択除去フィルター層中央
の中空部に連通するように、容器底部中央に設けること
が好ましい。[0008] Further, in order to press down the inner peripheral surface of the leukocyte selective removal filter layer and secure a hollow space, a leukocyte comprising a pipe having a mesh or a porous portion is provided in a central hollow portion of the leukocyte selective removal filter layer. It is preferable to provide a support in contact with the inner peripheral surface of the selective removal filter layer. The size of the hollow portion of the leukocyte selective removal filter layer is appropriately determined according to the size of the leukocyte selective removal filter layer, that is, the outer diameter and thickness of the leukocyte selective removal filter layer. In the present invention, the filter layer for selectively removing leukocytes is contained in a substantially similar cylindrical container, and both ends are sealed in a liquid-tight manner so that blood does not pass therethrough. For sealing, a material that is excellent in compatibility with blood and that does not leak liquid and that is suitable for sealing is used. Specifically, a known synthetic resin such as urethane can be used. The blood inlet may be provided at any position of the container as long as the blood to be processed can be supplied to the outer peripheral surface side of the white blood cell selective removal filter layer whose both ends are sealed. It is preferable that the filter is provided on the ceiling of the cylindrical container so that the blood to be processed is radially dispersed so that the blood flows uniformly into the outer peripheral surface of the filter layer and the filter layer for selectively removing leukocytes is used efficiently.
The blood outlet is preferably provided at the center of the bottom of the container so as to communicate with the hollow portion at the center of the hollow cylindrical leukocyte selective removal filter layer.
【０００９】以下図面を用いて本発明の白血球選択除去
フィルター装置について具体的に説明する。白血球選択
除去フィルター装置（１）は中空円筒状に巻かれた白血
球選択除去フィルター層（４）と血液入口（３）及び血
液出口（６）を有する容器（２）とからなる。中空円筒
状フィルター材はその両端が接着剤（５）によって液密
に封止されその外側と血液入口が、内側と血液出口がそ
れぞれ連続するよう容器内に収められる。被処理血液は
血液入口（３）より白血球選択除去フィルター装置
（１）内に入る。中空円筒状フィルター材（４）の両端
面は液密に封止されており血液が通過することはできな
い。そのため、血液はフィルター層の外周面を構成する
白血球選択除去フィルター層の最外層からフィルター材
の内部に徐々に浸透していきながら白血球が捕捉され、
中空円筒状フィルター材を通過し終ってフィルター材中
央部に集まりそこに連通する血液出口（６）を通って装
置外へ出て行く。フィルター材内部の血液流れは、白血
球選択除去フィルター層（７）に進入し白血球が捕捉除
去される流れとスペーサー層（８）に沿って渦巻き状に
中空円筒状フィルター材内周面へ向かって流れる２成分
の流れとが組み合わさった流れとなる。その結果血液
は、処理開始後すぐに中空円筒状フィルター材の外周部
と内部の両方に行き渡り結果として、局所的な急激な血
液凝固成分の活性化を抑制でき、処理開始より終了まで
の全時間にわたって効率的な白血球除去と高い血小板回
収性を実現できる。The leukocyte selective removal filter device of the present invention will be specifically described below with reference to the drawings. The selective leukocyte removal filter device (1) comprises a leukocyte selective removal filter layer (4) wound in a hollow cylindrical shape and a container (2) having a blood inlet (3) and a blood outlet (6). The hollow cylindrical filter material is liquid-tightly sealed at both ends with an adhesive (5), and housed in a container such that the outside and the blood inlet are continuous with the inside and the blood outlet, respectively. The blood to be treated enters the leukocyte selective removal filter device (1) from the blood inlet (3). Both end surfaces of the hollow cylindrical filter material (4) are sealed in a liquid-tight manner so that blood cannot pass therethrough. Therefore, blood gradually captures the leukocytes from the outermost layer of the leukocyte selective removal filter layer that constitutes the outer peripheral surface of the filter layer, while capturing the leukocytes,
After passing through the hollow cylindrical filter material, it collects at the center of the filter material and exits the apparatus through the blood outlet (6) communicating therewith. The blood flow inside the filter material enters the leukocyte selective removal filter layer (7) and is captured and removed and flows spirally along the spacer layer (8) toward the inner peripheral surface of the hollow cylindrical filter material. The flow is a combination of the two component flows. As a result, the blood spreads to both the outer peripheral portion and the inner portion of the hollow cylindrical filter material immediately after the start of the process, and as a result, local rapid activation of blood coagulation components can be suppressed, and the entire time from the start to the end of the process Over time, it is possible to realize efficient leukocyte removal and high platelet recovery.
【００１０】[0010]
【実施例】以下、実施例により本発明をより詳細に説明
する。The present invention will be described in more detail with reference to the following examples.
【実施例１及び比較例１】白血球選択除去フィルター層
は、平均繊維直径１．８μｍのポリプロピレン繊維より
なる不織布（目付７０ｇ／ｍ2、厚み０．３７ｍｍ）１
００ｇに、電子線を５０ｋＧｙ照射した後、１０％メト
キシジエチレングリコールメタクリレートエタノール溶
液３０Ｌに浸漬し、還流下７５℃でグラフト重合を実施
し、重合後２日間メタノールで洗浄したものを用いた。
グラフト前後の重量変化より求めたグラフトモノマー含
量は４％であった。上記により得られた白血球選択除去
フィルターを幅１５０ｍｍ、長さ６８０ｍｍとしたもの
を２枚重ねて用いた。スペーサー材には、ポリプロピレ
ン製メッシュ（厚み１．０ｍｍ、メッシュサイズ８）を
幅１５０ｍｍ、長さ８００ｍｍとして用いた。実施例１
では、以上の３枚を外周部においてメッシュが全外周面
を覆うように不織布と重ね、ポリプロピレン製の外径８
ｍｍの円筒型のメッシュを中心にして巻いて、外径３８
ｍｍの中空円筒状フィルター材（白血球除去フィルター
層がスペーサー材と接触する面積１０２０ｃｍ2）とし
た。比較例１では、スペーサー層を用いないで、白血球
選択除去フィルター２枚のみを中空円筒状に巻いて使用
した。これらのフィルター材の円筒軸方向両端をウレタ
ンで閉塞し、天井部と底部にそれぞれ血液入口と血液出
口を有する内径４１ｍｍ、長さ１５０ｍｍの円筒状容器
に中空円筒状フィルター材の外周面が容器に設けられた
血液入口に、内周面が容器に設けられた血液出口にそれ
ぞれ通じるように収め、白血球選択除去フィルター装置
とした。Example 1 and Comparative Example 1 A non-woven fabric made of polypropylene fibers having an average fiber diameter of 1.8 μm (weight per unit area: 70 g / m 2 , thickness: 0.37 mm) 1
After irradiating an electron beam with 50 kGy to 00 g, it was immersed in 30 L of a 10% methoxydiethylene glycol methacrylate ethanol solution, subjected to graft polymerization at 75 ° C. under reflux, and washed with methanol for 2 days after polymerization.
The graft monomer content determined from the weight change before and after grafting was 4%. Two leukocyte selective removal filters obtained as described above having a width of 150 mm and a length of 680 mm were used in an overlapping manner. As the spacer material, a polypropylene mesh (thickness 1.0 mm, mesh size 8) having a width of 150 mm and a length of 800 mm was used. Example 1
Then, the above three sheets are overlapped with a non-woven fabric so that the mesh covers the entire outer peripheral surface at the outer peripheral portion, and the outer diameter of the polypropylene is 8 mm.
mm around a cylindrical mesh with an outer diameter of 38 mm.
mm hollow cylindrical filter material (1020 cm 2 in area where the leukocyte removal filter layer contacts the spacer material). In Comparative Example 1, only two leukocyte selective removal filters were wound into a hollow cylindrical shape without using a spacer layer. Both ends of these filter materials in the cylindrical axis direction are closed with urethane, and the outer peripheral surface of the hollow cylindrical filter material is formed in a cylindrical container having an inner diameter of 41 mm and a length of 150 mm having a blood inlet and a blood outlet at the ceiling and the bottom, respectively. At the provided blood inlet, the inner peripheral surface was housed so as to communicate with the blood outlet provided in the container, respectively, to obtain a leukocyte selective removal filter device.
【００１１】[0011]
【実施例２及び比較例２】白血球選択除去フィルター層
の幅を２２５ｍｍ、ポリプロピレン製メッシュ（厚み
１．０ｍｍ、メッシュサイズ８）の幅を２２５ｍｍと
し、長さ２２５ｍｍの円筒状容器を用いる以外は、実施
例１と同様の白血球選択除去フィルター装置（白血球除
去フィルター層がスペーサー材と接触する面積１５３０
ｃｍ2 ）を作成し、実施例２とし、メッシュを用いない
以外は実施例２と同様の装置を作成し、比較例２とし
た。Example 2 and Comparative Example 2 Except for using a cylindrical container having a width of 225 mm, a width of a polypropylene mesh (thickness 1.0 mm, mesh size 8) of 225 mm and a length of 225 mm, the width of the filter layer for selectively removing leukocytes was 225 mm. The same leukocyte removal filter device as in Example 1 (the area 1530 where the leukocyte removal filter layer contacts the spacer material)
cm 2 ), and the same device as in Example 2 was used except that no mesh was used.
【００１２】実験例 各々の白血球選択除去フィルター装置に、ヘパリン
（５，０００Ｕ／Ｌ）を抗凝固剤として添加した牛の新
鮮血３乃至７Ｌ（白血球濃度４，５００〜８，３００個
／μＬ、血小板濃度１４４，０００〜４２０，０００個
／μＬ）を温度３７℃、流速５０ｍＬ／分で流し、白血
球選択除去フィルター装置前後の白血球及び血小板数の
濃度を分析し、白血球除去率及び血小板回収率を求め
た。白血球除去率は、白血球選択除去フィルター装置入
口側と出口側でそれぞれ血液を採取し白血球数をカウン
トし次式により算出し求めた。 白血球除去率（％）＝（入口側血液の白血球数−出口側
血液の白血球数）×１００／入口側血液の白血球数 血小板回収率は、白血球選択除去フィルター装置入口側
と出口側でそれぞれ血液を採取し血小板数をカウントし
次式により算出し求めた。 血小板回収率（％）＝出口側血液の血小板数×１００／
入口側血液の血小板数 結果を表１に示す。 Experimental Example 3 to 7 L of bovine fresh blood (leukocyte concentration: 4,500 to 8,300 cells / μL) in which heparin (5,000 U / L) was added as an anticoagulant to each leukocyte selective removal filter device. Platelet concentration of 144,000 to 420,000 cells / μL) at a temperature of 37 ° C. and a flow rate of 50 mL / min, and analyze the leukocyte and platelet count concentrations before and after the leukocyte selective removal filter device to determine the leukocyte removal rate and platelet recovery rate. I asked. The leukocyte removal rate was determined by collecting blood at the entrance and exit sides of the leukocyte selective removal filter device, counting the number of leukocytes, and calculating by the following equation. Leukocyte removal rate (%) = (the number of leukocytes in the blood on the inlet side-the number of leukocytes in the blood on the outlet side) × 100 / the number of leukocytes in the blood on the inlet side. The sample was collected, the number of platelets was counted, and calculated by the following equation. Platelet collection rate (%) = platelet count of blood on the outlet side x 100 /
Inlet blood platelet count The results are shown in Table 1.
【００１３】[0013]
【発明の効果】本発明の白血球選択除去フィルター装置
は、多量の血液を処理しても血液中の凝固成分を活性化
せず、血小板の活性化も抑制し、高い血小板回収率を達
成し、かつ所望量の血液から白血球を効率的に除去でき
る。According to the filter device for selectively removing leukocytes of the present invention, even if a large amount of blood is treated, the coagulation component in the blood is not activated, platelet activation is suppressed, and a high platelet recovery rate is achieved. In addition, leukocytes can be efficiently removed from a desired amount of blood.
【図１】本発明の白血球選択除去フィルター装置の１実
施態様を表す縦断面図である。FIG. 1 is a longitudinal sectional view showing an embodiment of a filter device for selectively removing leukocytes of the present invention.
【図２】本発明の白血球選択除去フィルター装置の１実
施態様を表す横断面図である。FIG. 2 is a cross-sectional view showing an embodiment of the leukocyte selective removal filter device of the present invention.
１ 白血球選択除去フィルター装置本体 ２ 円筒状容器 ３ 血液入口 ４ 中空円筒状フィルター材 ５ 接着剤 ６ 血液出口 ７ 白血球選択除去フィルター層 ８ スペーサー層 ９ 支持体 １０ 中空円筒状メッシュ DESCRIPTION OF SYMBOLS 1 Leukocyte selective removal filter main body 2 Cylindrical container 3 Blood inlet 4 Hollow cylindrical filter material 5 Adhesive 6 Blood outlet 7 Leukocyte selective removal filter layer 8 Spacer layer 9 Support body 10 Hollow cylindrical mesh
───────────────────────────────────────────────────── フロントページの続き Ｆターム(参考） 4C077 AA13 BB03 CC06 EE01 KK04 KK13 MM02 NN02 PP08 PP12 PP13 PP18 PP24 4D006 GA02 HA61 HA95 JA02B JA04B JA04C JA25B KE02P KE16P MA03 MA31 MA33 MA40 MB06 MC23X MC32X NA42 NA54 PA02 PB09 PB45 PB46 PC41 ──────────────────────────────────────────────────続 き Continued on the front page F-term (reference) 4C077 AA13 BB03 CC06 EE01 KK04 KK13 MM02 NN02 PP08 PP12 PP13 PP18 PP24 4D006 GA02 HA61 HA95 JA02B JA04B JA04C JA25B KE02P KE16P MA03 MA31 MA33 MA40 MB06 MC23X MC32PNA42 NA46
Claims (4)
μｍ未満であり、かつ繊維の表面にポリエチレングリコ
ール鎖を有するモノマー単位が共有結合により固定され
ている不織布からなる白血球選択除去フィルター層に血
液の流通が可能なシート状のスペーサー材が積層されて
反物状に円筒形状に巻かれてなる中空円筒状フィルター
材が、その両端面を封止された状態で血液入口と血液出
口とを有する円筒状容器に納められてなる白血球選択除
去フィルター装置であって、容器の血液入口は前記中空
円筒状フィルター材の外周面に通じる部位に、また容器
の血液出口は前記中空円筒状フィルター材の内周面に通
じる部位にそれぞれ設けられており、且つ前記スペーサ
ー材は前記中空円筒状フィルター材外周面に少なくとも
その外周端部を露出させていることを特徴とする白血球
選択除去フィルター装置。1. An average fiber diameter of 0.3 μm or more and 10.0 or more.
A sheet-like spacer material through which blood can flow is laminated on a leukocyte selective removal filter layer made of a nonwoven fabric having a length of less than μm and a non-woven fabric having a monomer unit having a polyethylene glycol chain fixed on the fiber surface by a covalent bond. A filter device for selectively removing white blood cells, wherein a hollow cylindrical filter material wound in a cylindrical shape in a shape is placed in a cylindrical container having a blood inlet and a blood outlet with both end surfaces sealed. A blood inlet of the container is provided at a portion communicating with the outer peripheral surface of the hollow cylindrical filter material, and a blood outlet of the container is provided at a portion communicating with the inner peripheral surface of the hollow cylindrical filter material, and the spacer material is provided. Wherein at least an outer peripheral end of the hollow cylindrical filter material is exposed on an outer peripheral surface thereof. Apparatus.
の内周面に露出していないことを特徴とする請求項１記
載の白血球選択除去フィルター装置。2. The filter according to claim 1, wherein the spacer material is not exposed on the inner peripheral surface of the hollow cylindrical filter material.
ー材と接触する面積が５００ｃｍ2 以上５００ｃｍ2未
満であることを特徴とする請求項１乃至２記載の白血球
選択除去フィルター装置。3. The leukocyte selective removal filter device according to claim 1, wherein an area where the leukocyte selective removal filter layer contacts the spacer material is 500 cm 2 or more and less than 500 cm 2 .
０．１ｍｍ以上５ｍｍ未満、スペーサー材の厚みが０．
５ｍｍ以上３．０ｍｍ未満で、かつ容器容量が１００ｍ
Ｌ以上５００ｍＬ未満であることを特徴とする請求項３
記載の白血球選択除去フィルター装置。4. The thickness of the filter layer for selectively removing leukocytes is 0.1 mm or more and less than 5 mm, and the thickness of the spacer material is 0.1 mm or more.
5 mm or more and less than 3.0 mm, and the container capacity is 100 m
4. The amount is not less than L and less than 500 mL.
The filter device for selectively removing leukocytes according to the above.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP37588398A JP4097826B2 (en) | 1998-12-21 | 1998-12-21 | Leukocyte selective removal filter device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP37588398A JP4097826B2 (en) | 1998-12-21 | 1998-12-21 | Leukocyte selective removal filter device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000185094A true JP2000185094A (en) | 2000-07-04 |
| JP4097826B2 JP4097826B2 (en) | 2008-06-11 |
Family
ID=18506210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP37588398A Expired - Fee Related JP4097826B2 (en) | 1998-12-21 | 1998-12-21 | Leukocyte selective removal filter device |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4097826B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003106518A1 (en) * | 2002-06-17 | 2003-12-24 | 旭メディカル株式会社 | Biocompatible polymer and filter for selectively eliminating leucocytes using the same |
| EP1444996A4 (en) * | 2001-10-16 | 2005-11-16 | Asahi Medical Co | Method of selectively eliminating virus and leukocytes, eliminating material and eliminating apparatus |
| JP2007527257A (en) * | 2003-07-03 | 2007-09-27 | フレゼニウス・ヘモケア・イタリア・ソシエタ・ア・レスポンサビリタ・リミタータ | Filter for removal of substances from blood products |
| KR101361452B1 (en) * | 2011-03-16 | 2014-02-11 | 코오롱인더스트리 주식회사 | Nonwoven Web for Blood Filter and Method for Manufacturing The Same |
| CN106178638A (en) * | 2015-03-03 | 2016-12-07 | 张家港高力特医疗器械有限公司 | Filter |
-
1998
- 1998-12-21 JP JP37588398A patent/JP4097826B2/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1444996A4 (en) * | 2001-10-16 | 2005-11-16 | Asahi Medical Co | Method of selectively eliminating virus and leukocytes, eliminating material and eliminating apparatus |
| JP2009018177A (en) * | 2001-10-16 | 2009-01-29 | Asahi Kasei Kuraray Medical Co Ltd | Material for selectively removing virus and leukocyte and use thereof |
| CN100457200C (en) * | 2001-10-16 | 2009-02-04 | 旭化成可乐丽医疗株式会社 | Virus and white blood cell selective removal method, removal material and remover |
| US7820371B2 (en) | 2001-10-16 | 2010-10-26 | Asahi Kasei Kuraray Medical Co., Ltd. | Method for removing viruses and leukocytes from blood using a surface comprising hydroxyl and polyethylene glycol groups |
| WO2003106518A1 (en) * | 2002-06-17 | 2003-12-24 | 旭メディカル株式会社 | Biocompatible polymer and filter for selectively eliminating leucocytes using the same |
| US7439013B2 (en) | 2002-06-17 | 2008-10-21 | Asahi Kasei Kuraray Medical Co., Ltd. | Biocompatible polymer and filter for selectively eliminating leucocytes using the same |
| JP2007527257A (en) * | 2003-07-03 | 2007-09-27 | フレゼニウス・ヘモケア・イタリア・ソシエタ・ア・レスポンサビリタ・リミタータ | Filter for removal of substances from blood products |
| KR101361452B1 (en) * | 2011-03-16 | 2014-02-11 | 코오롱인더스트리 주식회사 | Nonwoven Web for Blood Filter and Method for Manufacturing The Same |
| CN106178638A (en) * | 2015-03-03 | 2016-12-07 | 张家港高力特医疗器械有限公司 | Filter |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4097826B2 (en) | 2008-06-11 |
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